Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: "Can the Promise Be Kept?"

Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients' dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.

Can Double Fortification of Salt with Iron and Iodine Reduce Anemia, Iron Deficiency Anemia, Iron Deficiency, Iodine Deficiency, and Functional Outcomes? Evidence of Efficacy, Effectiveness, and Safety.

BACKGROUND: Anemia, iron deficiency, and iodine deficiency are problems of important public health concern in many parts of the world, with consequences for the health, development, and work capacity of populations. Several countries are beginning to implement double fortified salt (DFS) programs to simultaneously address iodine and iron deficiencies. OBJECTIVE: Our objective was to summarize the evidence for efficacy and effectiveness of DFS on the full range of status and functional outcomes and across different implementation and evaluation designs essential to successful interventions. METHODS: We conducted a systematic review and meta-analysis of published and gray literature examining the effects of DFS on nutritional status, cognition, work productivity, development, and morbidity of all population groups. We searched for articles in Medline, Embase, CINAHL, Cochrane Central Register, and ProQuest for randomized trials, quasi-randomized trials, and program effectiveness evaluations. RESULTS: A total of 22 studies (N individuals = 52,758) were included. Efficacy studies indicated a significant overall positive effect on hemoglobin concentration [standardized mean difference (95% CI): 0.33 (0.18, 0.48)], ferritin [0.42 (0.08, 0.76)], anemia [risk ratio (95% CI): 0.80 (0.70, 0.92)], and iron deficiency anemia [0.36 (0.24, 0.55)]. Effects on urinary iodine concentration were not significantly different between DFS and iodized salt. The impact on functional outcomes was mixed. Only 2 effectiveness studies were identified. They reported programmatic challenges including low coverage, suboptimal DFS quality, and storage constraints. CONCLUSIONS: Given the biological benefits of DFS across several populations in efficacy research, additional evaluations of robust DFS programs delivered at scale, which consider effective implementation and measure appropriate biomarkers, are needed.

Comparative Evaluation of Intestinal Absorption and Functional Value of Iron Dietary Supplements and Drug with Different Delivery Systems.

Iron is a fundament micronutrient, whose homeostasis is strictly regulated. Iron deficiency anemia is among the most widespread nutritional deficiencies and its therapy, based on dietary supplement and drugs, may lead to severe side effects. With the aim of improving iron bioavailability while reducing iron oral therapy side effects, novel dietary supplements based on innovative technologies-microencapsulation, liposomes, sucrosomes-have been produced and marketed. In the present work, six iron dietary supplements for different therapeutic targets were compared in terms of bioaccessibility, bioavailability, and safety by using an integrated in vitro approach. For general-purpose iron supplements, ME + VitC (microencapsulated) showed a fast, burst intestinal iron absorption kinetic, which maintained iron bioavailability and ferritin expression constant over time. SS + VitC (sucrosomes), on the other side, showed a slower, time-dependent iron absorption and ferritin expression trend. ME + Folate (microencapsulated) showed a behavior similar to that of ME + VitC, albeit with a lower bioavailability. Among pediatric iron supplements, a time-dependent bioavailability increase was observed for LS (liposome), while PIC (polydextrose-iron complex) bioavailability is severely limited by its poor bioaccessibility. Finally, except for SS + VitC, no adverse effects on intestinal mucosa vitality and barrier integrity were observed. Considering obtained results and the different therapeutic targets, microencapsulation-based formulations are endowed with better performance compared to the other formulations. Furthermore, performances of microencapsulated products were obtained with a lower iron daily dose, limiting the potential onset of side effects.

Efficacy of processed amaranth-containing bread compared to maize bread on hemoglobin, anemia and iron deficiency anemia prevalence among two-to-five year-old anemic children in Southern Ethiopia: A cluster randomized controlled trial.

BACKGROUND: Few studies have evaluated iron-rich plant-based foods, such as amaranth grain, to reduce anemia and iron deficiency anemia. Amaranth is rich in nutrients, but with high level of phytate. The objective of this trial was to evaluate the efficacy of home processed amaranth grain containing bread in the treatment of anemia, hemoglobin concentration and iron deficiency anemia among two-to-five year-old children in Southern Ethiopia. METHOD: Children with anemia (hemoglobin concentration <110.0g/L) (N = 100) were identified by random sampling and enrolled in a 1:1 cluster randomized controlled trial for six months in 2017. The amaranth group (N = 50), received 150g bread containing 70% amaranth and 30% chickpea, the amaranth grain was processed at home (soaking, germinating, and fermenting) to decrease the phytate level. The maize group (N = 50), received 150g bread, containing processed maize (roasted and fermented) to give a similar color and structure with amaranth bread. Hemoglobin, ferritin, and CRP were measured at baseline and at the end of intervention. Hemoglobin and ferritin values were adjusted for altitude and infection, respectively. Generalized estimating equation and generalized linear model were used to analyze the data. RESULT: In the last follow-up measure anemia prevalence was significantly lower in the amaranth group (32%) as compared with the maize group (56%) [adjusted risk ratios, aRR: 0.39 (95%CI: 0.16-0.77)]. Hemoglobin concentration estimate of beta coefficient was significantly higher in the amaranth group compared with the maize group [aß 8.9g/L (95%CI: 3.5-14.3)], p-value <0.01. The risk of iron deficiency anemia is significantly lower in the amaranth group [aRR: 0.44 (95%CI: 0.23-0.83)] in the intention to treat analysis but not significant in the complete case analysis. There was no significant difference between groups in iron deficiency [aRR: 0.81 (95%CI: 0.55-1.19)]. CONCLUSION: Processed amaranth bread had favorable effects on hemoglobin concentration and has the potential to minimize anemia prevalence. CLINICAL TRIAL REGISTRATION: Trial registry number: PACTR201705002283263 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2283.

Effect of lipid-based nutrient supplement-Medium quantity on reduction of stunting in children 6-23 months of age in Sindh, Pakistan: A cluster randomized controlled trial.

BACKGROUND: Chronic childhood malnutrition, or stunting, remains a persistent barrier to achieve optimal cognitive development, child growth and ability to reach full potential. Almost half of children under-five years of age are stunted in the province of Sindh, Pakistan. OBJECTIVE: The primary objective of this study was to test the hypothesis that the provision of lipid-based nutrient supplement-medium-quantity (LNS-MQ) known as Wawamum will result in a 10% reduction in risk of being stunted at the age of 24 months in the intervention group compared with the control group. DESIGN: A cluster randomized controlled trial was conducted in Thatta and Sujawal districts of Sindh province, Pakistan. A total of 870 (419 in intervention; 451 in control) children between 6-18 months old were enrolled in the study. The unit of randomization was union council and considered as a cluster. A total of 12 clusters, 6 in each study group were randomly assigned to intervention and control group. All children received standard government health services, while children in the intervention group also received 50 grams/day of Wawamum. RESULTS: Children who received Wawamum were found to have a significantly reduced risk of stunting (RR = 0.91, 95% CI; 0.88-0.94, p<0.001) and wasting (RR = 0.78, 95% CI; 0.67-0.92, p = 0.004) as compared to children who received the standard government health services. There was no evidence of a reduction in the risk of underweight (RR = 0.94, 95% CI; 0.85-1.04, p = 0.235) in the intervention group compared to the control group. Statistically significant reduction in anaemia in the intervention group was also found as compared to the control group (RR = 0.97, 95% CI; 0.94-0.99, p = 0.042). The subgroup analysis by age, showed intervention effect is significant in reduction of risk of stunting in younger children of aged 6-12 month (RR = 0.83, 95% CI; 0.81-0.86, p = <0.001) and their older peers aged 13-18 month- (RR = 0.90, 95% CI; 0.83-0.97, p = 0.008). The mean compliance of Wawamum was 60% among children. CONCLUSIONS: The study confirmed that the provision of Wawamum to children 6-23 months of age is effective in reducing the risk of stunting, wasting and anaemia. This approach should be scaled up among the most food insecure areas/households with a high prevalence of stunting to achieve positive outcomes for nutrition and health. This study was registered at clinicaltrials.gov as NCT02422953. Clinical Trial Registration Number: NCT02422953.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

Iron and prebiotic fortified flour improves the immune function of iron deficient women of childbearing age.

Micronutrient deficiencies (MNDs) are common worldwide, in both developing as well as developed countries. MNDs such as Iron Deficiency not only compromise the nutritional status of individuals but can also put them at an increased risk of developing various other diseases by negatively affecting their immunity. The objective of the current research was to determine the effects of prebiotics and iron fortificants on various immunoglobulins among iron deficient women belonging to childbearing age. To serve the purpose, a total of seventy five iron deficient women were selected and randomly divided into one control and four treatment groups. Accordingly, different types of fortified wheat flour were prepared, based on varying dosage of prebiotics and iron fortificants, to be fed to anemic women on daily basis for three months. Two iron salts (FeSO4 and NaFeEDTA) and two prebiotics (Galacto oligosaccharides and Inulin) were used to fortify wheat flour during the trials. Overnight fasted women were asked to give blood samples on monthly basis, up to three months. Four types of Immunoglobulins including IgA, IgE, IgG and IgM were determined at baseline, 30th, 60th and 90th day of trials using their respective protocols. The results of the study indicated that a statistically significant declining trend for IgA, IgE, IgG and IgM was present among the treatment groups (P-value < 0.05), compared to the control group. The study concluded that provision of iron and prebiotic fortified flour improved the immune function of iron deficient women.

Conventional and novel impacts of ferric citrate on iron deficiency anemia and phosphorus metabolism in rats.

Ferric citrate is an oral iron-based phosphate binder, being known to affect iron status and improve iron deficiency anemia (IDA) in chronic kidney disease (CKD) patients. We examined whether oral administration of ferric citrate could change iron status and improve anemia without affecting phosphorus metabolism in iron deficiency anemia rats. In Normal rat study, normal rats were fed a diet containing 0.3 or 3% ferric citrate for 11 days for setting the dose and administration period of ferric citrate. The effects of ferric citrate on iron status- and phosphorus metabolism-related parameters were evaluated using blood and urine samples. Next, an iron deficiency anemia was induced by feeding iron-depleted diet in rats. After 7 days of starting the iron-depleted diet, 0.3% ferric citrate was administered for 7 days by dietary admixture. Iron status- and phosphorus metabolism-related parameters were evaluated with blood and urine samples. In Normal rat study, 3% ferric citrate treatment increased serum iron level and transferrin saturation (TSAT), and decreased serum phosphorus level, intact fibroblast growth factor 23 (iFGF23) level, and urinary phosphorus excretion, but 0.3% ferric citrate treatment showed no effects. On the other hand, in Iron deficiency anemia rat study, 0.3% ferric citrate treatment increased iron status-related parameters and improved anemia, but did not show any apparent changes in phosphorus metabolism-related parameters. In conclusion, ferric citrate could have hematopoietic effects without affecting phosphorus metabolism, and could be a potential option for the treatment of IDA in patients without CKD.

A Novel School-based Intermittent Delivery System of Iron Supplements for Highly Marginalized Tarahumara Indigenous Women of Reproductive Age of Northern Mexico.

To develop a novel delivery scheme to bridge the Mexican health system with highly isolated indigenous communities by involving naturally occurring social links: households and boarding schools. This was a school-based placebo-controlled trial with a follow-up period of 16 weeks. Children whose mothers fulfilled the inclusion criteria for anemia acted as iron supplement carriers between schools and homes. Adherence was measured based on teachers' and mothers' records. An effectiveness sub-analysis assessed changes in biochemical profiles according to random allocation to either supplementation or placebo groups. There was an overall high adherence in both groups. Analyses revealed that schooling years, literacy, and walking times played a role in high adherence. Logistic regression showed that women had higher adherence odds on the basis of household size, walking times, and previous inclusion in supplement distributions. Adherence significantly decreased the proportion of anemia by 48.2% in the intervention group. The difference at baseline and endpoint significantly reduced the number of iron-deficient anemic women by 67.7% in the supplementation group. This delivery method is a valid alternative to the conventional efforts used to reach Tarahumara indigenous communities, and could also have the potential to be piloted to tackle other health issues hindering these marginalized communities.

Anemia no diabetes mellitus gestacional: implicações na instabilidade genômica / Anemia in gestational diabetes mellitus: implications for genomic instability

Introdução: Evidências têm mostrado uma associação entre anemia e Diabetes Mellitus. Contudo, a relação entre anemia e Diabetes Mellitus Gestacional (DMG) ainda não está bem estabelecida, bem como sua repercussão na instabilidade genômica. Portanto, objetivou-se verificar a associação entre anemia e instabilidade genômica em mulheres com DMG atendidas em um hospital universitário. Métodos: Estudo transversal com mulheres apresentando diagnóstico de DMG que realizaram pré-natal no Hospital Universitário de Santa Maria (RS). Informações referentes ao DMG, anemia e suplementação de ferro foram obtidas nos prontuários. A instabilidade genômica foi avaliada pelo ensaio de citoma em micronúcleos em células bucais (BMCyt). Resultados: Das 44 gestantes avaliadas, 28,6% apresentaram anemia e 79,5% foram suplementadas com ferro. Das gestantes que realizaram suplementação, 75,0% não apresentaram anemia gestacional. Níveis de hemoglobina não se associaram com a instabilidade genomica (p > 0,05), mas foi observada uma associação entre brotos nucleares e os níveis de glicemia (r = 0,977; p = 0,003). Conclusão: Não foi verificado associação entre anemia e instabilidade genômica em mulheres com DMG.(AU)

Introduction: There is evidence of an association between anemia and diabetes mellitus. However, the relationship between anemia and gestational diabetes mellitus (GDM) remains to be established, as well as its impact on genomic instability. Therefore, we aimed to examine the association between anemia and genomic instability in women with GDM treated at a university hospital. Methods: A cross-sectional study of women with a diagnosis of GDM who received prenatal care at the University Hospital of Santa Maria, southern Brazil. Data on GDM, anemia, and iron supplementation were obtained from medical records. Genomic instability was assessed by the buccal micronucleus cytome (BMCyt) assay. Results: Of 44 pregnant women evaluated, 28.6% had anemia and 79.5% received iron supplementation; of the latter, 75.0% did not have gestational anemia. Hemoglobin levels were not associated with genomic instability (p > 0.05), but an association was found between nuclear buds and blood glucose levels (r = 0.977; p = 0.003). Conclusion: There was no association between anemia and genomic instability in women with GDM.(AU)

Systematic review and meta-analysis of the effect of iron-fortified flour on iron status of populations worldwide.

OBJECTIVE: Assess the effectiveness of iron-fortified flour on iron status. DESIGN: Systematic review and meta-analysis. SETTING: Argentina, Australia, Azerbaijan, Bangladesh, Brazil, Cameroon, Chile, China, Costa Rica, Côte d'Ivoire, Denmark, India, Iran, Jordan, Kazakhstan, Kenya, Kuwait, Mongolia, Morocco, Norway, South Africa, Sri Lanka, Tajikistan, Thailand, UK, USA, Uzbekistan, Venezuela, Vietnam, and Zambia. PARTICIPANTS: Fifty-two articles (ninety-four trials) were examined. The main target groups were women, children, and infants/toddlers. The effects of different types of iron-fortified flour (wheat, maize, rice, soy, and beans) on iron status were examined. RESULTS: A random effects analysis of before-after studies showed that iron-fortified flour led to significant increases of mean haemoglobin level (3·360 g/l; 95 % CI: 0·980, 5·730) and mean serum ferritin level (4·518 µg/l; 95 % CI: 2·367, 6·669); significant decreases of anaemia (-6·7 %; 95 % CI: -9·8 %, -3·6 %) and iron deficiency (ID) (-10·4 %; 95 % CI: -14·3 %, -6·5 %); but had no significant effect on iron deficiency anaemia (IDA). A random effects analysis of controlled trials indicated that iron-fortified flour led to significant increases of mean haemoglobin level (2·630 g/l; 95 % CI: 1·310, 3·950) and mean ferritin level (8·544 µg/l; 95 % CI: 6·767, 10·320); and significant decreases of anaemia (-8·1 %; 95 % CI: -11·7 %, -4·4 %), ID (-12·0 %; 95 % CI: -18·9 %, -5·1 %), and IDA (-20·9 %; 95 % CI: -38·4 %, -3·4 %). CONCLUSIONS: Flour fortification with iron is an effective public health strategy that improves iron status of populations worldwide.

Evaluating the efficacy of a ferrous-ion-chelating peptide from Alaska pollock frame for the improvement of iron nutritional status in rats.

This study aimed to investigate the effects of ferrous-ion-chelating peptides from Alaska pollock frames (APFP-Fe) on iron deficiency in anaemic rats. We hydrolysed the Alaska pollock frames to obtain a peptide with an average molecular weight of 822 Da. The bioavailability of APFP-Fe was tested using animal experiments. Wistar rats were randomly divided into six groups: an iron deficiency control group, a normal control group, and iron deficiency groups treated with ferrous sulfate (FeSO4) or low-, medium-, or high-dose APFP-Fe. Rats in the iron deficiency groups were fed an iron-deficient diet to establish the iron deficiency anaemia (IDA) model. After the model was established, different iron supplements were given to rats once per day via intragastric administration for 21 days. The results showed that APFP-Fe had restorative effects, returning the body weight, weight gain, height, and haematological parameters in IDA rats to normal levels. In addition, compared with FeSO4, APFP-Fe promoted significant weight gain and effectively improved haemoglobin, serum iron and transferrin levels, and recovery of the capacity of iron binding with transferrin, especially at the medium and high doses. These findings suggest that APFP-Fe is an effective source of iron for improving the iron nutritional status in IDA rats and shows promise as a new source of iron supplementation.

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial.

BACKGROUND: The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). METHODS: This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6-59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sTfR) and body iron stores (BIS). We used Pearson's chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). RESULTS: The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4-56.5)% while that of ID and IDA were 55.7(48.6-62.5)% and 34.3(28.2-41.0)% when using sTfR criterion and 29.1(24.4-34.4)% and 28.9(23.7-34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9-20.3)% for FSMS-RUTF, 18.2(11.9-26.8)% for MSMS-RUTF and 24.5(15.8-35.9)% for PM-RUTF; p = 0.023] and IDA [7.9(3.4-17.3)% for FSMS-RUTF, 10.9(4.8-22.6)% for MSMS-RUTF and 20.5(10.7-35.5)% for PM-RUTF; p = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2-0.5) with p < 0.001 for FSMS-RUTF and 0.6 (0.3-1.0) with p = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. CONCLUSIONS: Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. TRIAL REGISTRATION: This study was registered on 15 April 2015 ( PACTR201505001101224 ).

Dietary Iron Intake and Anemia Are Weakly Associated, Limiting Effective Iron Fortification Strategies in India.

BACKGROUND: Anemia prevalence in India remains high despite preventive iron supplementation programs. Consequently, concurrent national policies of iron fortification of staple foods have been initiated. OBJECTIVES: This study evaluated the relation between dietary iron intake and anemia (hemoglobin <12 g/dL) in women of reproductive age (WRA; 15-49 y) with respect to iron fortification in India. METHODS: Data from 2 national surveys were used. Data on hemoglobin in WRA were sourced from the National Family Health Survey-4, whereas dietary intakes were sourced from the National Sample Survey. Adjusted odds for anemia with increasing iron intake were estimated, along with the effect of modulating nutrients such as vitamins B-12 and C, from statistically matched household data from the 2 surveys. The risks of inadequate (less than the Estimated Average Requirement for WRA) and excess (more than the tolerable upper limit for WRA) intakes of iron were estimated by the probability approach. RESULTS: The relation between iron intake and the odds of anemia was weak (OR: 0.992; 95% CI: 0.991, 0.994); increasing iron intake by 10 mg/d reduced the odds of anemia by 8%. Phytate and vitamin B-12 and C intakes modified this relation by reducing the odds by 1.5% when vitamin B-12 and C intakes were set at 2 µg/d and 40 mg/d, respectively. The additional intake of 10 mg/d of fortified iron reduced the risk of dietary iron inadequacy from 24-94% to 9-39% across states, with no risk of excess iron intake. Approximately doubling this additional iron intake reduced the risk of inadequacy to 2-12%, but the risk of excess intake reached 22%. CONCLUSIONS: Providing fortified iron alone may not result in substantial anemia reduction among WRA in India and could have variable benefits and risks across states. Geographically nuanced dietary strategies that include limited fortification and the intake of other beneficial nutrients should be carefully considered.

A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats.

BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.

Vitamin D3 supplementation for 8 weeks leads to improved haematological status following the consumption of an iron-fortified breakfast cereal: a double-blind randomised controlled trial in iron-deficient women.

The effect of 38 µg (1500 IU) daily vitamin D3 supplementation, consumed with an Fe-fortified breakfast cereal for 8 weeks, on haematological indicators in Fe-deficient female subjects was investigated. Fifty Fe-deficient subjects (plasma ferritin concentration <20 µg/l; mean age: 27·4 (sd 9·4) years) were randomised to consume an Fe-fortified breakfast cereal containing 9 mg of Fe daily, with either a vitamin D3 supplement or placebo. Blood samples were collected at baseline, interim (4 weeks) and post-intervention (8 weeks) for measurement of Fe and vitamin D status biomarkers. The effect of intervention was analysed using mixed-model repeated-measures ANOVA. Significant increases were observed in two main haematological indices: Hb concentration and haematocrit level from baseline to post-intervention in the vitamin D group but not in the placebo group. The increase from baseline to post-intervention in Hb concentration in the vitamin D group (135 (sd 11) to 138 (sd 10) g/l) was significantly higher compared with the placebo group (131 (sd 15) to 128 (sd 13) g/l) (P=0·037). The increase in haematocrit level from baseline to post-intervention was also significantly higher in the vitamin D group (42·0 (sd 3·0) to 43·8 (sd 3·4) %) compared with the placebo group (41·2 (sd 4·3) to 40·7 (sd 3·6) %) (P=0·032). Despite the non-significant changes in plasma ferritin concentration, this study demonstrates that 38 µg supplemental vitamin D, consumed daily, with Fe-fortified breakfast cereal led to improvement in Hb concentration and haematocrit levels in women with low Fe stores. These findings may have therapeutic implications in the recovery of Fe status in Fe-deficient populations at a healthcare level.

Effect of microalgae as iron supplements on iron-deficiency anemia in rats.

Microalgae are potential iron supplements for improving iron deficiency through an unknown mechanism. To analyze the increase in non-heme iron absorption caused by microalgae, six different microalgal feeds were prepared from Spirulina, Chlorella and Synechococcus sp. PCC 7002 as the main source of dietary iron (25 mg kg-1; denoted as H-Sp, H-Ch, and H-Sy, respectively) or as a partial source of dietary iron (5 mg kg-1; denoted as L-Sp, L-Ch, and L-Sy, respectively) to suppress iron-deficiency anemia in rats. The hemoglobin regeneration efficiencies in anemic rats were in the order ferric citrate (34.7 ± 1.8%) < H-Ch (49.9 ± 4.1%) ≈ H-Sy (50.6 ± 5.3%) ≈ L-Sp (46.9 ± 6.2%) ≈ L-Ch (43.1 ± 6.9%) ≈ L-Sy (43.5 ± 2.4%) ≈ FeSO4 (47.2 ± 4.9%) < H-Sp (54.8 ± 5.5%). The percentage content of intestinal nanosized iron in the H-Sp, H-Ch, and H-Sy treatment groups was significantly higher than that in the L-Sp, L-Ch, and L-Sy groups, and was significantly higher in the microalgal diet groups than in the ferric citrate group, providing strong evidence for nanosized iron supplementation from microalgae. Overall, microalgae, especially Spirulina, are functional iron nutritive fortifiers that can supply intestinal nanosized iron.

What Approaches are Most Effective at Addressing Micronutrient Deficiency in Children 0-5 Years? A Review of Systematic Reviews.

Introduction Even though micronutrient deficiency is still a major public health problem, it is still unclear which interventions are most effective in improving micronutrient status. This review therefore aims to summarize the evidence published in systematic reviews on intervention strategies that aim at improving micronutrient status in children under the age of five. Methods We searched the literature and included systematic reviews that reported on micronutrient status as a primary outcome for children of 0-5 years old, had a focus on low or middle income countries. Subsequently, papers were reviewed and selected by two authors. Results We included 4235 reviews in this systematic review. We found that (single or multiple) micronutrient deficiencies in pre-school children improved after providing (single or multiple) micronutrients. However home fortification did not always lead to significant increase in serum vitamin A, serum ferritin, hemoglobin or zinc. Commercial fortification did improve iron status. Cord clamping reduced the risk of anemia in infants up to 6 months and, in helminth endemic areas, anthelminthic treatment increased serum ferritin levels, hemoglobin and improved height for age z-scores. Anti-malaria treatment improved ferritin levels. Discussion Based on our results the clearest recommendations are: delayed cord clamping is an effective intervention for reducing anemia in early life. In helminth endemic areas iron status can be improved by anthelminthic treatment. Anti-malaria treatment can improve ferritin. In deficient populations, single iron, vitamin A and multimicronutrient supplementation can improve iron, vitamin A and multimicronutrient status respectively. While the impact of home-fortification on multimicronutrient status remains questionable, commercial iron fortification may improve iron status.

Iron therapy substantially restores qEEG maturational lag among iron-deficient anemic infants.

OBJECTIVE: To use quantitative electroencephalography (qEEG) to assess the impact of iron-deficiency anemia on central nervous system maturation in the first year of life. METHOD: Twenty-five infants (3-12 months old) presenting ferropenic anemia (IDA) and 25 healthy controls (CTL1), matched by age/gender with the former, were studied in two stages. Electroencephalogram during spontaneous sleep was recorded from all participants; the fast Fourier transform was calculated to obtain absolute power (AP) and relative power (RP) qEEG measures. In the first stage, a qEEG comparison between CTL1 and IDA was performed. Second stage consisted in comparing qEEG of the IDA infants before and after supplementation with iron (IDA-IS group), and comparing qEEG of the IDA-IS group with another control age-matched group (CTL2). Non-parametric multivariate permutation tests (NPT) were applied to assess differences between CTL1 and IDA groups, as well as IDA vs. IDA-IS, and IDA-IS vs. CTL2. RESULTS: More power in slow frequency bands and less power in fast frequency bands in 64% of IDA babies were observed. NPT evinced higher alpha AP and RP (P < 0.001), less theta AP, and less delta and theta RP in CTL1 than in IDA. After iron-restoration therapy, alpha AP and RP increased while theta AP and theta and delta RP decreased, reaching almost normal values. DISCUSSION: This work reveals CNS developmental delay through the study of qEEG (less rapid and more slow frequencies) which recovered significantly with iron supplementation. It is concluded that IDA constitutes a high risk factor for a lag of CNS maturation.